INDUCTION OF SEQUENCE-SPECIFIC DNA-BINDING FACTORS BY ERYTHROPOIETIN AND THE SPLEEN FOCUS-FORMING VIRUS

The signal transduction mechanism of erythropoietin (Epo), which regul ates growth and differentiation of erythroid cells, is still unclear. Recent studies showing the activation by various ligands of a group of proteins called Stat (signal transducers and activators of transcript ion) proteins raised the possibility that such proteins may also be in volved in the Epo signal transduction pathway. In this report, we show that Epo induces factors that specifically bind to the sis-inducible element and the gamma response region of the Fc gamma receptor factor I gene in the Epo-dependent mouse erythroleukemia cell line HCD-57. Th ese factors contain phosphotyrosine and antibodies against Stat1 and S tat3 proteins reacted with them. In HCD-57 cells infected with Friend spleen focus-forming virus, which now grow in an Epo-independent manne r, the DNA-binding factors were constitutively activated even in the a bsence of Epo. These results suggest that the factors induced by Epo c ontain components identical or related to known Stat proteins. It is a lso suggested that continuous activation of these DNA-binding factors may be responsible for the ability of spleen focus-forming virus to ab rogate the Epo-dependence of HCD-57 cells and cause erythroleukemia in susceptible mice. (C) 1995 by The American Society of Hematology.